title: The effect of GWAS identified BMI loci on changes in body weight among middle-aged Danes during a five-year period.
abstract: OBJECTIVE
  Genome-wide association studies have identified genetic variants associating with BMI, however, it is un-clarified whether the same variants also influence body weight fluctuations.
  
  
  METHODS
  Among 3,982 adult individuals that attended both a baseline and a five-year follow-up examination in the Danish Inter99 intervention study, a genetic risk score (GRS) was constructed based on 30 BMI variants to address whether it is associated with body weight changes. Moreover, it was examined whether the effect of lifestyle changes was modulated by the GRS.
  
  
  RESULTS
  The GRS associated strongly with baseline body weight, with a per risk allele increase of 0.45 (0.33-0.58) kg (P = 2.7 × 10(-12) ), corresponding to a body weight difference of 3.41 (2.21-4.60) kg comparing the highest (≥ 30 risk alleles) and lowest (≤ 26 risk alleles) risk allele tertile. No association was observed with changes in body weight during the five years. Changes in lifestyle, including physical activity, diet and smoking habits associated strongly with body weight changes, however, no interactions with the GRS was observed.
  
  
  CONCLUSIONS
  The GRS associated with body weight cross-sectionally, but not with changes over a five-year period. Body weight changes were influenced by lifestyle changes, however, independently of the GRS.
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: C H
authors.initials: CH
authors.lastname: Sandholt
authors.forename: K H
authors.initials: KH
authors.lastname: Allin
authors.forename: U
authors.initials: U
authors.lastname: Toft
authors.forename: A
authors.initials: A
authors.lastname: Borglykke
authors.forename: R
authors.initials: R
authors.lastname: Ribel-Madsen
authors.forename: T
authors.initials: T
authors.lastname: Sparso
authors.forename: J M
authors.initials: JM
authors.lastname: Justesen
authors.forename: M N
authors.initials: MN
authors.lastname: Harder
authors.forename: T
authors.initials: T
authors.lastname: Jørgensen
authors.forename: T
authors.initials: T
authors.lastname: Hansen
authors.forename: O
authors.initials: O
authors.lastname: Pedersen
mesh_terms: D000328:Adult; D000483:Alleles; D015992:Body Mass Index; D001835:Body Weight / Q000235:genetics*; D003430:Cross-Sectional Studies; D003718:Denmark; D004032:Diet; D005500:Follow-Up Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008019:Life Style; D016014:Linear Models; D008875:Middle Aged; D009043:Motor Activity; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012641:Selection, Genetic; D044465:White People / Q000235:genetics*